"In summary, we identified the SARS-CoV-2 spike as a COVID-19 virus factor that interrupts p53 binding to MDM2 in cancer cells and demonstrated the suppressive effect of SARS-CoV-2 spike on p53 signaling in cancer cells. Correlated to the inhibition of p53 signaling, the short-term expression of spike caused an altered DNA damage response through altered levels of γ-H2AX after DNA damage in cells, altered sensing in the damage response to cisplatin. Importantly, the p53-dependent DNA damage induction of growth arrest and apoptotic targets p21(WAF1) and TRAIL Death Receptor DR5 was significantly attenuated under different experimental conditions with spike and this was associated with greater cell viability in the presence of spike and chemotherapy treatment. As loss of p53 function is a known driver of cancer development and confers chemo-resistance, our study provides insight into cellular mechanisms by which SARS-CoV-2 spike may be involved in reducing barriers to tumorigenesis during and post SARS-CoV-2 infections."
© 2024 Zhang and El-Deiry. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.